Human, animal and synthetic materials are currently used in medical procedures to augment tissue or repair or correct tissue defects. To be optimum, such materials should not migrate and should promote the regeneration of normal tissue, repopulating with the host's cells, revascularizing, and integrating with the patient's own tissue without triggering an inflammatory response that results in the degradation or resorption of the material. Additionally, the manner of delivery of such material, e.g. by surgical procedure or by injection, may significantly affect the clinical applications of the material, the ease of use by the physician and the cost of the procedure.
Injectable collagen and other materials have been used clinically for a wide variety of pathological and cosmetic applications in the fields of reconstructive surgery, dermatology, oncology, otolaryngology and urology. Currently, the most widely used form of injectable collagen is derived from crosslinked bovine Type I collagen. In human clinical applications the effect of this xenogenic transplant is resorption by the human host. Patients receiving these xenogenic grafts are susceptible to an immune response to the animal collagen, requiring prescreening for existing antibodies. Examples of such materials may be found in U.S. Pat. Nos. 4,582,640; 5,104,957; 5,728,752; and 5,739,176.
Human collagen that may be injected is currently available and sold under the tradenames Autologen® and Dermologen® and is manufactured by Collagenesis. This material it typically derived from autologous collagen obtained during elective surgery or allogenic collagen from cadavers. The starting material is dissociated by mechanical means and chemically treated to remove all noncollagenous proteins. The collagen is treated with additional chemicals to mask or crosslink the adverse effects of these damaged and exposed collagen fibers. More information with regard to this technology may be found in U.S. Pat. Nos. 4,969,912 and 5,332,802.
AlloDerm®, produced by LifeCell Corporation, is an acellular tissue matrix which is produced from normal human skin using processing techniques established to remove the epidermis and cells within the dermis without significantly altering the normal biochemistry and molecular architecture of the connective tissue matrix. The resulting product is in a freeze-dried form allowing extended shelf life and ease of shipping without degradation or loss of the normal tissue matrix components. AlloDerm® is used clinically to repair or replace damaged or inadequate tissues. Reported applications for AlloDerm® include: full thickness burn injury, replacement of lost gingiva due to periodontal disease, reconstructive surgical applications involving the replacement of lost tissue or restoration of normal surface contours of skin damaged due to injury or aging neurosurgical application to replace lost dura and in urological applications such as bladder slings and pelvic floor reconstruction. AlloDerm® has been reported to integrate at the graft site where it is rapidly repopulated with the normal milieu of host cells. A reported benefit of AlloDerm® is that it maintains the structure and biochemistry of the tissue matrix, promoting normal tissue regeneration. Studies have indicated that AlloDerm® retains decorin, hyaluronic acid, chondroitin sulfates, nidogen, growth factors and other biochemical proteins present in normal soft tissues. Additionally, AlloDerm® is reported to contain the basement membranes of vascular channels and the orientation of elastin and collagen fibers of the starting dermal tissue. For these reasons it is believed that the structure and biochemistry of the AlloDerm® matrix promotes tissue regeneration. Reducing sheet AlloDerm® to a particulate suitable for injection should extend the beneficial properties of AlloDerm® to several new applications.
Methods presently used to produce currently available injectable collagen materials include mechanical disruption of the starting material in its wet, hydrated state. However, when such processes are carried out on intact autograft, allograft or xenograft tissue, damage to the matrix occurs such that following transplantation a foreign body response and rapid resorption of the tissue matrix occurs. Further, microscopic and histological analysis of material processed in such a manner exhibit mechanical disruption of the collagen fibers. Mechanical disruption of dried human or animal tissue at non-cryogenic temperatures is believed to create a similar disruption of the collagen fibers, resulting in a foreign body response by the recipient and resorption of the material.
Thus there exists an unmet need for a method of making an intact particulate acellular tissue matrix from acellular tissues.